Press Release - Oct 18, 2012
The Future of Cancer Treatment: First-of-its-kind Self-Assembled Nanoparticle for Targeted and Triggered Thermo-Chemotherapy
Excitement around the potential for targeted
nanoparticles (NPs) that can be controlled by stimulus outside of the body for cancer
therapy has been growing over the past few years. More specifically, there has been
considerable attention around near-infrared (NIR) light as an ideal method to
stimulate nanoparticles from outside the body. NIR is minimally absorbed by
skin and tissue, has the ability to penetrate deep tissue in a noninvasive way
and the energy from NIR light can
be converted to heat by gold nanomaterials for effective thermal ablation of
diseased tissue.
In new research from Brigham and Women's Hospital
(BWH), researchers describe the design and effectiveness of a first-of-its-kind,
self assembled, multi-functional, NIR responsive gold nanorods that can deliver
a chemotherapy drug specifically targeted to cancer cells and selectively
release the drug in response to an external beam of light while creating heat
for synergistic thermo-chemo mediated anti-tumor efficacy. The study is electronically published in Angewandte Chemie International
Edition.
"The design of this gold nanorod and its
self-assembly was inspired by nature and the ability of complimentary strands
of DNA to hybridize on their own without imposing complicated chemical
processes on them," explained Omid Farokhzad, MD, an anesthesiologist, director of the Laboratory
of Nanomedicine and Biomaterials at BWH, and senior author
of this study. "Each functionalized DNA
strand individually, and the self assembled components as a system, play a
distinct yet integrative role resulting in synergistic targeted and triggered
thermo-chemotherapy capable of eradicating tumors in our pre-clinical models."
One DNA strand is attached to the gold nanorod and
the complementary strand is attached to a stealth layer and a homing molecule
that keeps the system under the radar of the immune system while targeting it directly
to cancer cells. When the DNA strands come together, the targeted gold nanorod
is formed and the double stranded DNA serves as the scaffold for binding the
chemotherapy drug, doxorubicin, which can be released in response to NIR light
that concurrently results in generation of heat by the gold nanorods.
"This new platform is comprised of three distinct
functional components and each plays a role in contributing to the triple punch
of triggered thermotherapy, controlled doxorubicin release, and cancer cell targeting,"
explained Zeyu Xiao, PhD, a postdoctoral fellow at BWH and lead author of this
study.
To demonstrate the robust capability of this nanorod
system, Farokhzad and colleagues used a pre-clinical model to evaluate the in vivo
anti-tumor efficacy in two different tumor models and four different groups
with different drug regiments, each group varying in weight and tumor size. Researchers
administrated an injection of the novel, self-assembled nanoparticle and then
10 minutes post-injection, the tumors were irradiated using NIR light that
activated the nanoparticle using the gold nanorod and created heat. The results showed that this platform successfully
delivered heat and anti-cancer drugs and synergistically eradicated tumors.
"Thermal ablation is already commonly used in cancer
treatment," said Dr. Farokhzad. "What is
extremely exciting about this platform is that we are able to selectively target
cancer cells and then hit the tumor twice: first with a controlled release of a
chemotherapy drug and then secondly with triggered induction of heat from the
activation of the gold nanorod. And all
this can be done noninvasively."
Researchers acknowledge that more research is
necessary in other pre-clinical models before testing the safety and efficacy
of this platform in human clinical trials.
This research was supported by the National
Institutes of Health under grant number CA151884 and the David Koch-Prostate
Cancer Foundation Program in Cancer Nanotherapeutics. O.C.F. has financial
interest in BIND Biosciences, Selecta Biosciences, and Blend Therapeutics,
biopharmaceutical companies that are developing therapeutic nanoparticles.
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